Deletion of glycogen synthase kinase-3β in cartilage results in up-regulation of glycogen synthase kinase-3α protein expression."Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/β-catenin. The two GSK-3 proteins, GSK-3α and GSK-3β, display both overlapping and distinct roles in different tissues. Pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth[i.e. growing taller], accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some effects of phosphatidylinositide 3-kinase inhibition in this system, in agreement with the antagonistic role of these two kinases in response to signals such as IGF. Cartilage-specific deletion of the Gsk3b gene in mice has minimal effects on skeletal growth or development. Compensatory up-regulation of GSK-3α protein levels in cartilage is the likely cause for this lack of effect."

"GSK-3α and GSK-3β [have both overlapping and distinct roles]"

"Tibia treated with [an inhibitor that inhibits both GSK3alpha and Beta] grew 31% more than controls over the 6 d of organ culture"

"Inhibition of GSK-3 promotes long bone longitudinal growth by increasing bone formation."<-But is this only growth rate or adult height?

"GSK-3α, which is more widely expressed in the growth plate, is the predominate GSK-3 form targeted by inhibition of the PI3K pathway through the resting and proliferating zones, whereas GSK-3β is the main target in the prehypertrophic zone."

"The effect of the PI3K inhibitor was partially recovered by the combination with the GSK-3 inhibitor"<-Meaning some of the benefits of the PI3K pathway on height growth are mediated by it's inhibition of GSK-3.

"The cyclin-dependent kinase inhibitor p57 is both a marker of prehypertrophic chondrocytes and promotes cell cycle exit in the growth plate. In tibia organ culture, inhibition of GSK-3 or dual treatments of GSK-3 and PI3K inhibitors greatly increased the zone of p57 protein expression in the prehypertrophic zone"

"up-regulation of GSK-3α compensates for the loss of GSK-3β in cartilage."<-So we have to inhibit GSK-3alpha in addition to GSK-3Beta.